To investigate the pathogenesis of various autoimmune diseases, We have explored the mechanism of polyclonal B cell activation in several aspects. We have utilized the culture system with immobilized mAb to CD3 molecular complex, in which B cells are very potently activated through contact with T cells. First, we have revealed that the CD18 molecule plays an important role for the T cell -B cell contact in this system. Second, to investigate the mechanism of autoantibody production, the extent and nature of IgM-RF precursors and anti-DNA precursors within normal B cells were examined by utilizing immobilized mAb to CD3 and Staphylococcus aureus (SA). The precursor frequency of anti-DNA producing cells (0.019-0.097 per 10^2 B cells) were almost the same as that of IgM-RF producing cells (0.025-0.104 per 10^2 B cells) in cultures stimulated with immobilized anti-CD3. Of note, addition of SA increased the precursor frequency of IgM-RF producing cells, but not that of anti-DNA producing ce
… Morells, in anti-CD3 stimulated cultures. These data support the conclusion that the precursors of anti-DNA producing cells have different activation requirement from those of IgM-RF producing cells. Third, the immunoregulatory functions of human T cell subpopulation were examined. The results suggest that the suppressor-effector function of human T cells may rather be related with the stages of the post-thymic differentiation as evidenced by the T cell subsets, such as T4 and T8 cells. Moreover, it has also been shown that IL2 plays an important role in the generation of suppressor-effector T cells. These observation may explain at least in part the mechanism of the deficient suppressor T cell activity in systemic lupus erythematosus. Finally, we have revealed that the expression of FcgammaRL on monocytes from patients with rheumatoid arthritis was increased. This finding may well be related the production of IgMRF, since both SA and FcgammaRI bind Fc portion of IgG.みられる免疫異常が根本的に異なるものであるということが認識された。リウマチ因子産生細胞・抗DNA抗体産生細胞の活性化の機序が明らかにされた点,およびサプレッサ-T細胞の誘導メカニズムが明らかにされた点が的研究の大きな成果であり,これにより自己免疫疾患の病因・病態の解明に大きく貢献するものと考えられる。みられる免疫異常が根本的に異なるものであるということが認識された。リウマチ因子産生細胞・抗DNA抗体産生細胞の活性化の機序が明らかにされた点,およびサプレッサ-T細胞の誘導メカニズムが明らかにされた点が的研究の大きな成果であり,これにより自己免疫疾患の病因・病態の解明に大きく貢献するものと考えられる。 Less